Multivalency protein-carbohydrate interactions

J. C. Sacchettini, L. G. Baum, and C. F. Brewer, Multivalent protein-carbohydrate interactions. A new paradigm for supermolecular assembly and signal transduction, Biochemistry, 40 (2001) 3009-3015. 

Figure 13.1 A schematic representation of a variety of processes that are mediated by multivalent protein-carbohydrate interactions.

Multivalent protein-carbohydrate interactions mediate many intercellular recognition processes. In order to study and to modulate multivalent protein-carbohydrate interactions, many carbohydrate-functionalized frameworks and systems have been synthesized. The glycodendrimer is one important glycosystem that has been used to study lectin binding. For our work, glycodendrimers based on the PAMAM framework are ideal because of the inherently flexible nature of PAMAM and because of the ease with which PAMAMs can be functionalized with carbohydrates. 

The described examples, where more than one carbohydrate is attached to a synthetic framework, foreshadow the advances that we should expect in research involving multivalent protein-carbohydrate interactions. Functionalization of multivalent... 

This model predicts that the formation of additional contacts should give exponential affinity increases because only the first binding event exacts a translational entropy penalty. However, the entropic costs related to conformational flexibility are likely to be much higher for a multivalent protein-carbohydrate interaction. 

Thiourea Linkages. Attachment of saccharide units to the surface of PAMAM through thiourea linkages offers one of the most efficient ways to develop multivalent ligands quickly and efficiently for the study of protein-carbohydrate interactions. 

R. J. Pieters, Maximising multivalency effects in protein-carbohydrate interactions, Org. Biomol. Chem., 7 (2009) 2013-2025. 

Owing to the weakness of carbohydrate receptor-protein interactions, in order to attain biological meaningful affinities for the receptor, carbohydrates very often need to be clustered and expressed in multiple copies. For this purpose glycodendrimers, which are multivalent glycoconjugates with well-defined chemical structures, have received recent attention for their considerable potential as tools for studying cell-surface protein-carbohydrate interactions, because of the affinity enhancement obtained by multivalency. 

Glycodendrimers are useful for generating the multivalency important for protein-carbohydrate interactions and for many biomedical applications. Nevertheless, the formation of these structures is most often a laborious task. The... 

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